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The Holy Grail of Hepatocyte Culturing and Therapeutic Use

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Strategies in Regenerative Medicine

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Authors and Affiliations

  1. Technical University Munich, Department of Traumatology, Ismaningerstr. 11, 81829 Munich, Germany

    Andreas K. Nussler

Authors
  1. Andreas K. Nussler
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  2. Natascha C. Nussler
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  3. Vera Merk
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  4. Marc Brulport
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  5. Wiebke Schormann
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  6. Ping Yao
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  7. Jan G. Hengstler
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Corresponding author

Correspondence to Andreas K. Nussler .

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Editors and Affiliations

  1. School of Pharmacy &, Biomolecular Sciences, University of Brighton, Lewes Road, Brighton, BN2 4GJ, United Kingdom

    Matteo Santin

Additional information

Questions/Exercises

  1. 1.

    Explain the actual legal situation to perform hepatic cell isolation and transplantation.

  2. 2.

    Why is it not allowed to use isolated liver cells for cell transplantation from patients that underwent tumor therapy?

  3. 3.

    Describe the isolation process of liver cells from large and small liver specimens and describe possible differences and similarities of both procedures.

  4. 4.

    Which types of bioreactors/artificial liver devices exist? Explain their advantages and disadvantages.

  5. 5.

    Describe the advantages to use human liver cells instead of non-human cells in drug developments.

  6. 6.

    Give at least five examples for human hepatocyte transplantation and explain different clinical diseases in which hepatocyte transplantation has been applied.

  7. 7.

    In the chapter about “reporter studies for cell fusion”, we describe two studies resulting in contradictory conclusions (Alvarez-Dolado versus Harris). Design a specific experiment that could dissolve the discrepancy.

  8. 8.

    A scientist presents a new stem cell derived “hepatocyte-like cell type”. He demonstrates expression of 17 “hepatocyte-factors” by conventional RT-PCR and 12 by immunostaining and concludes: ‘The high number of hepatocyte factors expressed in our stem cell derived cells proves that they are indeed hepatocytes.’ Do you agree? Which additional experiments would you suggest to determine the proximity of these cells to genuine hepatocytes? How can interindividual differences between hepatocytes from different donors be considered?

  9. 9.

    Can unmodified embryonic stem cells be used for cell therapy of metabolic liver diseases? (answer: no; risk of teratoma formation).

  10. 10.

    Give typical characteristics of a human hepatocyte-like cell and discuss differences and similarities with “native” human hepatocytes.

Ten Key Publications

  1. 1.

    Dorko K, Freeswick PD, Bartoli F, Cicalese L, Bardsley BA, Tzakis A, Nussler AK (1994) A new technique for isolating and culturing human hepatocytes from whole or split livers not used for transplantation. Cell Transplant 3:387–395

  2. 2.

    Hengstler JG, Brulport M, Schormann W, Bauer A, Hermes M, Nussler AK, Fandrich F, Ruhnke M, Ungefroren H, Griffin L, Bockamp E, Oesch F, von Mach MA (2005) Generation of human hepatocytes by stem cell technology: definition of the hepatocyte. Expert Opin Drug Metab Toxicol 1:61–74

  3. 3.

    Li AP (2001) Screening for human ADME/Tox drug properties in drug discovery. Drug Discov Today 6:357–366

  4. 4.

    Michalopoulos GK, DeFrances M (2005) Liver regeneration. Adv Biochem Eng Biotechnol 93:101–134

  5. 5.

    Michalopoulos GK, DeFrances MC (1997) Liver regeneration. Science 276:60–66

  6. 6.

    Nussler A, Konig S, Ott M, Sokal E, Christ B, Thasler W, Brulport M, Gabelein G, Schormann W, Schulze M, Ellis E, Kraemer M, Nocken F, Fleig W, Manns M, Strom SC, Hengstler JG (2006) Present status and perspectives of cell-based therapies for liver diseases. J Hepatol 45:144–159

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    Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP (1999) Bone marrow as a potential source of hepatic oval cells. Science 284:1168–1170

  8. 8.

    Ruhnke M, Ungefroren H, Nussler A, Martin F, Brulport M, Schormann W, Hengstler JG, Klapper W, Ulrichs K, Hutchinson JA, Soria B, Parwaresch RM, Heeckt P, Kremer B, Fandrich F (2005) Differentiation of in vitro-modified human peripheral blood monocytes into hepatocyte-like and pancreatic islet-like cells. Gastroenterology 128:1774–1786

  9. 9.

    Seglen PO (1976) Preparation of isolated rat liver cells. Methods Cell Biol. 13:29–83

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    Strom SC et al. (1998) Large scale isolation and culture of human hepatocytes. In: Franco D, Boudjema K, Varet K (eds) Ilots de Langerhans et hepatocytes: Vers une utilisation therapeutique, pp 195–205

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Nussler, A.K. et al. (2009). The Holy Grail of Hepatocyte Culturing and Therapeutic Use. In: Santin, M. (eds) Strategies in Regenerative Medicine. Springer, New York, NY. https://doi.org/10.1007/978-0-387-74660-9_9

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